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Cited by 302Gestational Diabetes Research and ManagementBirth, Development, and HealthObesity, Physical Activity, Diet

Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study

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on behalf of the HAPO Follow-up Study Cooperative Research Group, Lowe, William L., Lowe, Lynn P., Kuang, Alan, Catalano, Patrick M., Nodzenski, Michael, Talbot, Octavious, Tam, Wing-Hung +14 more·2019·Diabetologia
DOI 10.1007/s00125-018-4809-6PMC PMC6421132
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Abstract

Aims/hypothesisMaternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.MethodsThe HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75 g OGTT at ~28 weeks gestation 10–14 years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including: (1) being overweight/obese according to sex- and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA1c values during pregnancy.ResultsFully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA1c measures, ORs for each child adiposity outcome were in the range of 1.05–1.16 for maternal fasting glucose, 1.11–1.19 for 1 h glucose, 1.09–1.21 for 2 h glucose and 1.12–1.21 for HbA1c. Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls.Conclusions/interpretationExposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.

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  • Children born to mothers with gestational diabetes have higher rates of childhood adiposity and impaired glucose tolerance at ages 10 to 14 than children born to mothers without gestational diabetes.

    “Children born to women with GDM have increased incidence of childhood adiposity and development of IGT in children aged 10 to 14 years compared with children born to mothers without GDM.56,57”

    From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [56]

    The Discussion (page unavailable) says that, among HAPO Follow-up Study children aged 10–14, maternal GDM was associated with higher risk of obesity and other adiposity measures, though not with the combined overweight/obese outcome. The Methods > Outcomes section (page unavailable) lists adiposity outcomes, not impaired glucose tolerance; the paper does not support the IGT part of the claim. (LLM, conf=0.88)

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  • GDM increases the child's susceptibility to developing obesity and impaired glucose tolerance in the future.

    “The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study 1 and subsequently follow‐up studies 2 , 3 , 4 have reported that gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes, which increases the mother's susceptibility to developing type 2 diabetes, and the child's susceptibility to developing obesity and impaired glucose tolerance in the future 3 , 4 , 5”

    From Clinical challenges in early pregnancy in Japan: An update on gestational diabetes (2024) · cites this paper as [3]

    The Introduction and Discussion report an association between GDM or higher maternal glucose and childhood obesity or adiposity, including in children aged 10–14 years. They do not report impaired glucose tolerance in the children, and the paper describes an association rather than establishing that GDM causes either outcome. (LLM, conf=0.87)

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  • In 10- to 14-year-old offspring, maternal hyperglycemia was linearly and positively correlated with increased total fat percent, sum of skinfolds, and the incidence of obesity after adjusting for maternal BMI during pregnancy.

    “In 10- to 14-year-old offspring, maternal hyperglycemia was linearly and positively correlated with increased total fat percent (measured by air displacement plethysmography), sum of skinfolds, and the incidence of obesity after adjusting for maternal BMI during pregnancy [8].”

    From Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications (2022) · cites this paper as [8]

  • Gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes.

    “The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study 1 and subsequently follow‐up studies 2 , 3 , 4 have reported that gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes, which increases the mother's susceptibility to developing type 2 diabetes, and the child's susceptibility to developing obesity and impaired glucose tolerance in the future 3 , 4 , 5”

    From Clinical challenges in early pregnancy in Japan: An update on gestational diabetes (2024) · cites this paper as [3]

  • GDM increases the mother's susceptibility to developing type 2 diabetes.

    “The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study 1 and subsequently follow‐up studies 2 , 3 , 4 have reported that gestational diabetes mellitus (GDM) is associated with various adverse pregnancy outcomes, which increases the mother's susceptibility to developing type 2 diabetes, and the child's susceptibility to developing obesity and impaired glucose tolerance in the future 3 , 4 , 5”

    From Clinical challenges in early pregnancy in Japan: An update on gestational diabetes (2024) · cites this paper as [3]

    The Introduction discusses maternal diabetes during pregnancy in relation to childhood adiposity, and the Discussion reports an association between maternal glucose and childhood adiposity. Neither addresses whether GDM increases a mother's later risk of type 2 diabetes. Searches for subsequent maternal or postpartum type 2 diabetes found no supporting passage in our copy; page numbers were not available. (LLM, conf=0.76)

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Research works printed but not linked: 1

  1. [22]Van Buuren S, Groothuis-Oudshoorn K (2011) Multivariate imputation by chained equations in R. Journal of Statistical Software 45: 1– 67

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Authors
on behalf of the HAPO Follow-up Study Cooperative Research Group, Lowe, W. L., Lowe, L. P., Kuang, A., Catalano, P. M., Nodzenski, M., Talbot, O., Tam, W.-H., Sacks, D. A., McCance, D., Linder, B., Lebenthal, Y., Lawrence, J. M., Lashley, M., Josefson, J. L., Hamilton, J., Deerochanawong, C., Clayton, P., Brickman, W. J., Dyer, A. R., Scholtens, D. M., & Metzger, B. E.
Affiliations
  • Northwestern University (US)
  • MetroHealth Medical Center (US)
  • Chinese University of Hong Kong (HK)
  • Kaiser Permanente (US)
  • Royal Victoria Hospital (GB)
  • National Institutes of Health (US)
  • Tel Aviv University (IL)
  • University of Toronto (CA)
  • Rajavithi Hospital (TH)
  • Manchester Academic Health Science Centre (GB)
Corresponding author
Metzger, Boyd E.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2019-01-15
Volume
62
Issue
4
Pages
598-610
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-018-4809-6
PMC
PMC6421132
OpenAlex
W2911007152
Semantic Scholar
2e46697541db330189cda46dc419697dbff59a5c
Cited by
294
References
44
Citations by year
2026: 28 · 2025: 38 · 2024: 54 · 2023: 44 · 2022: 58 · 2021: 29 · 2020: 32 · 2019: 10
FWCI
35.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • National Center for Advancing Translational Sciences (UL1TR001422)
  • National Institute of Diabetes and Digestive and Kidney Diseases (1U01DK094830)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords
childhood adiposity, hyperglycemia in pregnancy, maternal type 2 diabetes, gestational diabetes mellitus, HbA1c, oral glucose tolerance test, offspring obesity, skinfold thickness, waist circumference, body fat percentage
MeSH terms
Adult, Blood Glucose, Child, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Hyperglycemia, Male, Maternal Age, Pregnancy, Pregnancy Complications, Pregnancy in Diabetics, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Body Mass Index, Diabetes, Gestational, Adiposity, Overweight, Waist Circumference, Pediatric Obesity

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